Manufacture of 1-halogen-aryl-thiazoles



Patented Sept. 20, 1932 STATES PATENT .FFI

WINFBID HENTRICI-I AND MAX- HARDTMANN, OF WI ESDORE-ON-THE-REINE, J'OSEFHILGEB, OF COLOGNE-MULHEIM, AND WERNER ZERWECK, FRANKFGRIS-ON-THE-MAlN-FECHENHEIM, GERMANY, ASSIGNOES TO: I. GQFARIBENINDUSTRIE AKTIEN-GESELLSCHLAFT, 0F FRANKFORT-ONrTEE-MAIN, GERMANY, A CQRI POIRATION OFGERMANY MANUFACTURE OF I-HALOGEN-AR-YL-THIAZOLES No Drawing. Applicationfiled April 25, 1929, Serial No. 358,156, and in' Germany April 30,1928.

The present invention relates to a process of preparingl-halogen-aryl-thiazoles, more particularly it relates to compounds ofthe general formula:

N q \O-Hal wherein R stands for an aromatic ring which may besubstituted by any substituent, and Hal stands for a chlorine or bromineatom.

According to our invention, l-halogenbenzothiazoles andl-halogen-naptho-thiazoles are obtainablein excellect yields by reacting upon a l-hydroxy-benzothiazole or a lmercapto-benzothiazole(compare for instance Teppema, Journal of the American Chem. Soc, volume49, page 17 53 and 1780 (1927)) or the corresponding naphtho-thiazoles,said compounds being represented by the general formula:

wherein R stands for an aromatic ring, such as a benzene or naphthalenenucleus, which may be substituted by alkyl, a nitro or carboxylic acidgroup and m stands for an oxygen or sulfur atom, with a phosphorushalogen compound of' the formula: P-Hal wherein Hal stands for achlorine or bromine atom, two halogen atoms of which may be substitutedby a sulfur or oxygen atom, for example phosphorus pentachloride,phosphorus pentabromide', phosphorus-oxychloride and phosphorussulfo-chloride at a temperature from about (1., to about100 (3., or 130C. respectively in the case of the phos phor-bromine compounds, and ifdesired in an inert organic solvent, such as chlorobenzone andsolventnaphtha.

Since the halogen in the 1-position can be exchanged very readilyagainst any desired compounds, possessing a mobile hydrogen atomattached to, for example a nitrogen, oxygen, sulfur or carbon atom, agreat number of technically valuable substances become readilyaccessible by the newprocess. These substances are intended to findapplication as intermediate products for dyestufis, for pharmaceuticalpreparations or, for combating pests, as accelerators, for vulcanizationand the like, I i a The invention is illustrated by the follow- 7 ingexamples, but is not restricted thereto:

Example 1.167 parts by weight of l-mercaptobenzothia zole' 7 sure. Thephosphorus sulfo chloride distils up to 135 (1, then a small amount ofundee composed addition compounds follows, which can be decomposed by arepeated distillation, and at 248 C. the l-chloro-benzothiazole distilsaThe total yield 'amountsto over 95%. EmampZe2.l51'parts by weight ofl-hydroxy-benzothiazole v a are heated with 230 parts by weight ofphosphorus pentachloride and 100200 parts ,by

weight of phosphorus oxychloride (as'dilut ing agent) for 3 hours at1007 C. After thisjtime the thiazole and the phosphorus nentachloride gocompletely into solution. The solution is distilled in vacuo and theadphorus chloride, which appears as intermediateproduct, decomposes at abath temperature 0f1l00e200 C. Themixture of phosdition compoundofchloro-thiazole and phospounds follows, which can be decomposed by arepeated distillation and at 248 C. the} The, total 1-chlorobenzothiazole distils. yield amounts to over 95%. f

Example 3.--181 parts by weight of} 4- methyl-l-mercaptobenzothiazole(Teppema, loc. cit.) I 1 are heated with 225 parts by weight of phosphorus pentachloride-(if desired with the addition of phosphorussulfo'-chloride).for 3-4 hours at about 100C. Afterthis time thereaction mixture forms amelt,;on which only a few solid particlesstillfloat. Prolonged heating increases the undissolved portion andreduces the wield more and more in consequence of the occurrence of abye-reaction. The melt is first distilled in vacuo, then fractionationis again efi'ected at ordinary pressure. Thei-methyl-l-chlorobenzothiazole; solidifies in the receiver. It melts at40-47" C. Its boiling point lies at 266C. and in the vacuum cf the waterpump it boils at 132 C. The yield is almost theoretical.

According to the process ofthis-example other .l-cholorbenzothiazoleswith .an alkyl 2 group substituted. in the'benzene nucleuscan alsoibeobtained. J 1 I 9 Example (w-212 parts weight of the 5- nitrol-mercaptobenzothiazole which is read ily. obtainable by nitration of1-mercaptobenothiazole (c. f. 'Teppema, loc. cit.) .are heated with 230parts by. weight of phosphorus pentachloride and 200 'parts'by weightof, phosphorus sulfo chloride for 6 hours at 95 C. After this timesolution is complete. The meltisnow heated in vacuo to a bathtemperature of 180 C. in orderito eliminate phosphorus chloride. Theresidue is dissolved in hot alcohol and filtered. On cooling the5-nitro-1-chloro-benzothiazole separates. A further portion can berecovered from the mother liquon The 5-nitro-1- chlorobenzothiazolemelts at 190 C. and when heated with aniline, it gives a phenylaminocompound of the melting point 247 C. Its properties are those of'thesubstance obtained by Hofmann (locxcit) by nitration of cholorphenylmustard 7 oil (that is 1= chlorobenzothiazole). i a 7 According to theprocess of thisexample the corresponding cholorbenzothiazolessubstituted with halogen in the benzene nucleus or naphthalene nucleuscan be obtained} in an analogous manner thel-cholorbenzothiazolel-carboxylic acid chloride can be obtained by theaction'of rather more than two molecules of phosphorus pentachloride onthe carboxylic acid of the formula:

described by Teppema (10c. cit.)

Weclaim: 7 r .v

' 1. The process which comprises reacting upon a compound of the generalformula:

wherein R stands for an aromatic nucleus whichmay be substituted byalkyl, a nitro or carboxylic acid, group and w stands for an oxygen orsulfur atom with a phosphorus halogen compound of the formula: P Halwherein Hal stands for a chlorine or bromine atom, two of which halogenatoms may be substitutedby anatom of the group consisting of oxygen and.sulfur, at a temperaturebetween 80 and 130 C; with the addition of asolvent.

3 The process which comprisesreacting upon a compound of thegeneralformula r j 's wherein y stands for hydrogen, alkyl, a nitrogroup or a carboxylic acid group and m stands for an oxygen or sulfuratom, with a phosphorus halogen compound of the for mula: P-Hal whereinHal stands fora chlorine or bromine atom, 1 two of which halogenatomsmay be substituted by an atom of the group consisting of. oxygenand sulfur,

wherein y stands for hydrogen, alkyl, a nitro group 'or a carboxylicacid group and 0a; stands for an oxygen or sulfur atom, with aphosphorus halogen compound of the formula: P Hal wherein Hal stands fora chlorine or bromine atom, two of which halogen atoms may besubstituted by an atom of the group consisting of oxygen and sulfur, ata temperature between and 130 C. with the addition of a solvent.

5. The process which comprises reacting upon a compound of the formula:

with a phosphorus halogen compound of the formula: P Hal wherein Halstands for a chlorine or bromine atom, two of which halogen atoms may besubstituted by an atom of the group consisting of oxygen and sulfur, ata temperature between 80 and 130 C.

6. The process which comprises reacting upon a compound of the formula:

O: O SH with a phosphorus halogen compound of the formula: PHal whereinHal stands for a chlorine or bromine atom, two of which halogen atomsmay be substituted by an atom of the group consisting of oxygen andsulfur, at a temperature between 80 and 130 C. with the addition of asolvent.

7 The process which comprises reacting upon a compound of the formula:

with phosphorus pentachloride at a temperature between and C.

8. The process which comprises reacting upon a compound of the formula:

with phosphorus pentachloride at a temperature between 90-100 C. withthe addition of phosphorus oxychloride as diluting agent.

In testimony whereof we have hereunto set our hands.

WINFRID HENTRIOH. MAX HARDTMANN. J OSEF HILGER. WERNER ZERWECK.

